MOLECULAR PROPERTIES OF CASEINS AND ALLERGENICITY

CANDREVA ANGELA M.; DOCENA GUILLERMO H.; PETRUCCELLI SILVANA

Caseins: Properties, Functions and Health Implications

Nova Science Publishers, Inc.

Lugar: New York; Año: 2016;

Cow´s milk allergy (CMA) is an aberrant reaction to the in principle harmless cowmilkproteins (CMP). CMA is themost frequent cause of food allergy in childhood andseveral reasons areresponsible of highest prevalence, among then earlyintroduction of CMP in the infantdiet. Both plant and animal allergens belongto a relative small group of structuralrelated proteins thatshare some physicochemical characteristicssuch as proteolysis resistance,aggregation tendency and thermostability. Ligandbinding activity is alsodetected in some animal allergen such the major CMPallergens caseins (CAS) andalso the whey proteins: alpha lactalbumin (ALA) andbeta-lactoglobulin (BLG). Whole CAS fraction, known as Bos d 8allergen, isheterogeneous and recently has been reclassified by WHO/IUISAllergenNomenclature Sub-Committee into four separate groups: alpha S1-CAS (Bosd9.0101), alpha S2-CAS (Bos d 10.0101), beta-CAS (Bos d 11.0101) andkappa-CAS(Bos d 12.0101). Primary sequences of alpha S1-CAS, alpha S2-CAS, andbeta-CAS areconsistent with a common ancestor and rapidly evolution of thesessecretorycalcium-binding phosphoproteins with an important role as source of aminoacids,calcium and phosphorus for offspring. In contrast, the kappa-CASexhibitfeatures that demonstrate a separate origin and function sincestabilizes themicelle structure. Comparison of CAS from different mammalsshowed amino acidsequence homologies of up to 90%, what explain extensivecross-reactivity and selectivesensitizations found when cow milk is replacewith milk of other farm animals such as sheep,goat, buffalo, mare, etc.Usingsynthetic peptides, recombinant CAS fragments and proteomic approaches, mainCASepitopes has been mapped and also its molecular intra and interspeciesdiversityhas been characterized. Most of these epitopes are linear what distinguishCASof other allergen that have conformational epitopes. Unexpected someIgE-bindingregion of bovine CAS caseins showed a high degree of similarity withthe human CAS.This is unforeseen, since proteins with 62% sequence identity toa humanhomolog are rarely allergenic. CAS kept the secondary structure uponheating up to 55°C what indicatethermal stability like other allergens. CAS is known to retain their allergenicity after pasteurization.CASare easilydigested in the gut while most food allergens are proteaseresistance. Mice modelsfor allergy are currently used to investigate theintrinsic properties thatpromote allergenicity. Using crude and pasteurizedfraction of ALA, BLG andCAS, to oral challenge CMP sensitized mice it has beenshown that soluble ALA andBLG but not insoluble CAS trigger anaphylaxis whendelivered orally. Inaddition, pasteurization caused aggregation of ALA and BLG,reducing its uptakeby intestinal epithelial cells and abilty to triggershypersensitivity response.Then aggregated proteins, such as CAS, are bettersensitizing antigens for foodallergies, but soluble antigens are required forsymptom provocation. This informationsuggests the importance of the tendency toform aggregates in allergen featuresand highlights one of importantcharacteristic of CAS to trigger allergenicitythat should be taking account inpreventive and therapeutics treatments for CMA.